In most ‘hand osteoarthritis (OA)’ surveys, a number of subjects is discerned with the clinics of erosive finger joint OA (Zhang W et al, EULAR ESCISIT group, 2008). These patients show symmetrical and severe destructive changes in more than a few of their interphalangeal (IP) joints. The progressive nature of this disease has been well documented (Verbruggen G, Veys E M, 1996).
In these IP joints the classical picture of ‘non-erosive’ OA is complicated by manifest erosive changes, which precede a period in which repair phenomena in the ‘eroded’ finger joints lead to the generation of a new subchondral plate covered by cartilaginous tissue. On the roentgenpicture the erosive changes in the affected IP joints include the disappearance of the joint space within a relatively short period of time. Concurrently with or shortly after the disappearance of the articular cartilage, substantial osteolytic areas may emerge in the subchondral bone and the subchondral plate becomes eroded. The joint space of the affected IP joint may then appear enlarged and utterly disordered. These destructive phases are always followed by repair or remodeling. Then, new irregular sclerotic subchondral plates are formed, and in between these, a new joint space becomes visible. The subchondral osteolytic areas gradually disappear. Huge osteophytes are formed during this phase. No further evolution is seen in remodeled IP joints.
In osteoarthritis, which is a degenerative joint disease, endogenous disease promoting factors are released in a dense extracellular matrix surrounding the chondrocyte. This dense extracellular matrix makes it almost impossible for therapeutics (e.g. antibodies or receptor antagonists) to scavenge this endogenous disease promoting factors before they reach their target. In contrast, in inflammatory joint diseases such as rheumatoid arthritis, exogenous factors (like TNF ) are released from an inflamed synovium and therapeutics (anti-TNF monoclonal antibodies or receptor antagonists) will scavenge these exogenous factors before they reach the articular cartilage cell to provoke an autodestructive (IL-1) cascade.
5-10% of subjects with “erosive hand” osteoarthritis (OA) show severe destructive changes in their interpalangeal (IP) finger joints.
The classical picture of ‘non-erosive’ OA in these IP joints is complicated by destructive changes before naturally occurring repair in the ‘eroded’ finger joints leads to the generation of new remodeled articular tissues. The 3 anatomical structures in the IP finger joints: the subchondral bone, the subchondral bone plate and the synovial joint space are affected in a way distinguishing the radiographic picture from that of other destructive rheumatic joint diseases, e.g. psoriatic or rheumatoid arthritis. Also, the radiographic picture is absolutely different from that of the classic forms of osteoarthritis.
Assessing abnormalities radiologically is one of the most powerful means available to the clinical investigator. Radiographs, which serve as a permanent record of disease progression at different times, can be compared simultaneously. A set of radiographs from individual patients can be “blinded” and randomly assigned a sequence, to achieve greater objectivity in scoring. Standardized patient positioning and radiographic techniques, as well as the use of fine-detail screen-film combinations, have also improved the sensitivity and reproducibility of radiographic scoring.
Recently, the digital imaging techniques have been applied to the study of bone and joint disease. Improvements in hardware and software for digital image workstations have led to the development of a number of picture archiving and communication systems, which have been reported to increase clinical efficiency and are now well accepted by radiologists. The advantages of digital image formats are facilitated archiving and retrieval, image processing and display and remote transmission.
EP1046374 published on 25 Oct. 2000, describes “the Promosco X-posure System” to determine Bone Mineral Density (BMD) using radiogrammetry. Where BMD measures are particularly useful in diagnosing osteoporosis, it has no predictive power as to disease progression and/or in monitoring treatment response in arthritic conditions.
A publication of Sharp J. T. et al. (2000) relates to the feasibility of using computer programs to measure the radiographic joint space width and estimate erosion volumes in the hands of patients with rheumatoid arthritis (RA).
In a publication of Böttcher J. et al. (2005) the above mentioned “the Promosco X-posure System” has been complemented with a semi-automated analysis of Joint Space Width (JSW) as a new diagnostic approach in RA.
An article of Finckh A. et al. (2006) provides an alternative algorithm to determine JSW in RA.
Hence, for RA there are several scoring systems available that determine the RA lesions. However, these systems are unable to score osteochondral repair in synovial joints after e.g. anti-inflammatory treatment of subjects with RA.
A publication of Van 't Klooster R. et al (2008) provides an automatic measurement of the joint space width in finger joints in hand radiographs, to quantify OA in forty subjects with primary non-erosive OA. Buckland-Wright C. et al (1991, 1999 and 2004) uses radiography to detect changes in subchondral bone and the advancement in the zone of calcified cartilage that occur with the onset and progression of hand OA. These last documents each give methods that focus on different aspects of non-erosive OA and are unable to reflect or score disease onset and progression typical for erosive OA of the interphanlangeal finger joints.
Verbruggen G et al (1998, 2002) provides a system to score the progression of hand erosive OA based on consecutive pathological phases recognized in the course of the disease: A stationary or “S” phase OA joint (a non-erosive OA joint) can enter the phase where the joint space has disappeared (the “J” phase). Then the OA joint can progress to the phase where manifest erosive changes have occurred (the “E” phase), followed by the final repair/remodeling or “R” phase. In this scoring system numerical values were attributed to the different phases and the system only allowed to record a change from one pathological phase to the other over a substantial 3 year period of time (Verbruggen G et al, 1998, 2002). This analytical system did not allow discriminating between smaller changes in anatomical progression e.g. within the same pathological phase.
However, destruction and reconstruction of the subchondral bone, the subchondral bone plate and the synovial joint space in the IP finger joints can show considerable variation in morbidity and can be observed through all the successive pathological phases of erosive OA. Considerable overlap of destruction and repair can occur in the succeeding phases of the disease.
Hence, for erosive hand OA there is a need for an appropriate scoring system that is able to quantify disease progression especially early in the course of the disorder and that can assess the reparative changes after drug treatment or in the late stages of the disease and thus can score disease progression or repair in shorter follow-up periods.
The present invention solves the above described problems.
Grading the presence of normal tissue in at least 3 well-defined tissue compartments (subchondral bone plate, subchondral bone and joint space) on a stepwise or continuous incremental scale and summation of these at least 3 subdomain scores allows to generate an overall score for an IP finger joint in whichever phase of the disease. The scoring method is significantly sensitive to changes over time and allows changes in IP joint scores in small study populations to be calculated over short follow-up times. The scoring system is particularly valuable to monitor natural or drug-modified disease progression in erosive interphalangeal finger joint OA. Furthermore it can serve as a clinical tool to identify and value drugs with anticatabolic and/or repair promoting potential in erosive interphalangeal finger joint OA.